Heavy metals are increasingly significant pollutants of the human environment. Outside of occupational settings, they enter the body primarily through food and water; a fraction of the ingested metals is then absorbed and may exert severe toxic effects in selected target organs. It is important, therefore, to understand and possibly to control the intestinal absorption of the metals; this constitutes the long-term goal of the proposed work. The immediate goal is to characterize the sites involved in metal absorption, and to elucidate the nature of metal-metal interaction in the intestine. The main metal to be studied is cadmium, and the rat will serve as experimenal animal, in continuation of ongoing research. Two main approaches to these objectives are planned: 1) An attempt will be made to determine which intestinal segment in vivo is primarily responsible for Cd absorption. For this purpose, Cd absorption will be measured after its injection into various segments in the living animal. Once such a segment has been identified, it can be isolated for study of absorption processes in the intact animal. A particular problem will be elucidation of the binding sites responsible for the intramucosal trapping of metals during their absorption. 2) Because the first step in metal absorption by the chosen segment involves reaction with brush border, fragments of the brush border membrane will be isolated in vitro, and their capacity to bind metals will be measured. Competition between several metals for binding will be evaluated and compared to possible competition for absorption in the living animal. Attempts will also be made to determine the chemical nature of the binding sites by treatment of the membranes with proteases or phopholipase, or by addition of specific chemical reagents.